Cultures of normal metazoan cells show a finite proliferative ability, which may be related to the aging process in metazoa. The ciliate protozoan Paramecium tetraurelia shows a clonal life cycle functionally analogous to that of normal metazoan cells. Starting at fertilization, a clone goes through a series of phases, ending in clonal senility and eventual death. Because they possess many advantages in terms of culturing, handling and amenability to genetic analysis, the aging process in paramecia can be considered to be a useful model system for the apparently similar processes seen in metazoan cells. Possibilities for the cause of clonal senility in P. tetraurelia fall into 2 groups: 1) the accumulation of damage in the genome in the macronucleus, and 2) the development of a cytoplasmic (extra-nuclear) debility, which will not support the function of even a "good" nucleus. Evidence can be found to support either possibility. I propose to investigate clonal senility with a view to resolve whether the nucleus or the cytoplasm of a cell is the primary cause of the senility defects seen. The central approach will be to use microinjection techniques to transfer cytoplasm or macronuclei from young cells to old cells and vice versa. For example, an old macronucleus can be injected into an enucleated young cell, and the life-span of the injected cell's clone measured and compared with appropriate controls. If the macronucleus is the primary site of aging, then the clone should have a short life-span, due to the old nucleus. If the cytoplasm is the primary site of aging, then this clone will have a long life-span, due to its young cytoplasm. By separating the cytoplasm from the nucleus in these tests, one should be able to assess independently their individual contributions to the aging process.